tbuckley/cabot-search huggingface dataset:
P1684: NO INCREASE IN THROMBIN GENERATION OR D-DIMER LEVELS AFTER ANTI-SARS-COV-2 VACCINES INCLUDING IN THOSE WITH ANTI-PLATELET FACTOR 4 ANTIBODIES
Authors: L. Garabet, A. Eriksson, E. Tjønnfjord, M. Kringstad Olsen, H. K. Jacobsen, C. Tøvik Jørgensen, Å.-B. Mathisen, M.-C. Mowinckel, M. T. Ahlen, I. Hausberg Sørvoll, K. Daae Horvei, S. Leiknes Ernstsen, I. Jenssen Lægreid, P. M. Sandset, W. Ghanima
Journal: HemaSphere (2022)

Background: Anti-SARS-CoV-2 adenoviral-vectored-DNA vaccines have been linked to a rare but serious thrombotic post-vaccine complication called the vaccine-induced immune thrombotic thrombocytopenia (VITT). VITT has raised concerns regarding the possibilities of increased thrombotic risk and thrombocytopenia after anti-COVID-19 vaccines. Aims: To investigate whether anti-SARS-CoV-2 vaccines can cause thrombocytopenia, coagulation activation and increased thrombin generation leading to a hypercoagulable state. Methods: In this study, 567 healthcare personnel were included from two hospitals in Norway after obtaining informed consent. Of these, 521 were recruited 11-57 days post-vaccination with the first dose of ChAdOx1-S (Vaxzevria®, AstraZeneca, UK) vaccine, and 46 were recruited prospectively prior vaccination with an mRNA vaccine, either elasomeran (Spikevax, Moderna, n=38) or tozinameran (Comirnaty, Pfize-BioNTech, n=8). In the latter group, samples were acquired before and 1-2 weeks after vaccination. In addition to pre-vaccination samples, 56 unvaccinated healthy blood donors were recruited as controls (total n=102). Thrombin generation and D-dimer were analyzed. Results: None of the participants developed thrombosis/VITT. 12% reported cutaneous bleeding after vaccination, however, none had thrombocytopenia with platelet count <100·109/L. There were no significant differences in D-dimer or the parameters of thrombin generation between the two vaccine groups and the controls (Table 1). Anti-PF4/polyanion antibodies (optical density ≥0.4) were found in 11 of 513 individuals vaccinated with ChAdOx1-S vaccine (2.1%). None of the controls had anti-PF4/polyanion antibodies. Thrombin generation and D-dimer were not found to be higher in the ChAdOx1-S vaccinated individuals with anti-PF4 antibodies than in those without anti-PF4/polyanion antibodies. No differences in thrombin generation between the ChAdOx1-S group and the mRNA group. The median D-dimer level was slightly higher in the ChAdOx1-S group than the mRNA group, but both were within the normal range (Table 1). Thrombin generation and D-dimer showed no changes after mRNA vaccination compared with baseline. Image:Summary/Conclusion: Anti-COVID-19 vaccines, both ChAdOx1-S and mRNA vaccines, did not lead to an increase in thrombin generation or D-dimer compared with controls, not even in the ChAdOx1-S vaccinated individuals with anti-PF4/polyanion antibodies. No differences were found between ChAdOx1-S and mRNA vaccines, and no increase in thrombin generation or D-dimer was found after mRNA vaccines compared with baseline levels. Our results are reassuring in the sense that no subclinical activation in the coagulation system was observed with these vaccines.
P1546: ACTIVATE-KIDST: MITAPIVAT IN CHILDREN WITH PYRUVATE KINASE DEFICIENCY WHO ARE REGULARLY TRANSFUSED
Authors: R. F. Grace, P. D. Tyler, M. Little, P. A. Kosinski, V. Beynon
Journal: HemaSphere (2022)

Background: Pyruvate kinase (PK) deficiency is a rare hereditary chronic hemolytic anemia caused by PKLR gene mutations. Clinical management includes regular red blood cell (RBC) transfusions; some children require splenectomy, which carries a risk of sepsis and thrombosis. PK deficiency is associated with serious complications, regardless of transfusion status. There are no approved pharmacotherapies in children; there is an unmet need for therapies targeting the underlying cause of hemolysis. Mitapivat (AG-348), a first-in-class, oral, allosteric activator of the RBC PK enzyme, demonstrated significant reduction in transfusion burden in adults with PK deficiency who are regularly transfused (ACTIVATE-T NCT03559699); 37% achieved a transfusion reduction response and 22% achieved a durable transfusion-free status that was maintained in the long-term extension study (NCT03853798). Safety and efficacy data support the evaluation of mitapivat in children with PK deficiency who are regularly transfused. Aims: Report the design of the phase 3 ACTIVATE-KidsT study (NCT05144256), which will evaluate the efficacy and safety of mitapivat in children with PK deficiency who are regularly transfused. Methods: ACTIVATE-KidsT, a global, multicenter, double-blind, placebo-controlled study, will stratify 45 children by age and splenectomy status. A minimum of 6 patients per age group (1 to <6, 6 to <12, and 12 to <18 years) will be randomized (2:1) to receive mitapivat or placebo. The double-blind portion includes an 8-week dose titration period and a 24-week fixed-dose period; a 5-year open-label extension will follow. Study drug will be administered at a range of 1–50 mg twice daily, depending on age and weight; dosing categories are derived from pharmacokinetic modeling data of adults with PK deficiency. Key inclusion criteria: ≥2 mutant PKLR alleles with ≥1 missense mutation, ≥6 transfusion episodes in the past year. Key exclusion criteria: R479H homozygosity, presence of 2 non-missense mutations in PKLR without a missense mutation, or prior stem cell transplantation. The primary endpoint is transfusion reduction response, defined as ≥33% reduction in transfusion volume during the fixed-dose period normalized by weight and actual study drug duration, compared with historical transfusion volume standardized by weight and to 24 weeks. Secondary endpoints will assess the effect of mitapivat on transfusion-free status, iron metabolism and overload, safety, quality of life, and pharmacokinetics. Results: Global site recruitment is in-progress; an update on recruitment and patient enrollment will be provided. Summary/Conclusion: The ACTIVATE-KidsT study of children with PK deficiency who are regularly transfused will evaluate the efficacy and safety of mitapivat, a potential disease modifying pharmacotherapy that targets the underlying enzymatic defect of PK deficiency.
PB1855: LACK OF MUTATIONS IN TNFRSF13B (TACI) IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: N. Giannakoulas, E. Georgiadi, S. Makri, G. Tsinti, F. Kalala, M. Speletas
Journal: HemaSphere (2022)

Background: Chronic Lymphocytic Leukemia (CLL) is the most common leukemia in the Western world. Many molecular mechanisms and functionally relevant biological programs seem to be of importance in the pathogenesis of the disease, with emphasis on the antigenic drive within a specific microenvironment along with the apoptotic pathways failure that may have eventually a role in the survival of CLL cells. Transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) is a major regulator in the immune responses and is encoded by TNFRSF13B gene. TACI is mainly expressed by mature B cells, inhibits B cell expansion and promotes the differentiation and survival of plasma cells. TNFRSF13B germline mutations contribute to the pathogenesis and phenotype of common variable immunodeficiency (CVID), a disease entity that usually complicated by B cell malignanices. Aims: The purpose of the present study was to analyze the mutational status of the TNFRSF13B gene, since the majority of mutations are presented in these exons. Methods: Fifty CLL patients (30 men and 20 women) were included in the study. The median age at diagnosis was 70 years. (range 40-80). Twenty-four patients (48%) were treated naïve, while the remaining twenty-six patients (52%) have already received at least one prior therapy. Four out of thirty one patients (13%) were at high risk group according to available molecular data. The molecular analysis of TNFRSF13B genes was performed by was PCR sequencing. Results: There was no pathogenic mutation detected in the samples analyzed. We identified the common intronic polymorphism, g.28376A> C, c.445 + 25A> C, rs2274893 intron variant (30 patients in the 50 studied) and the silent mutation rs 35062843 (p.P97=, in 3 patients). Comparing our results with data of the Exac database (displaying the prevalence of polymorphisms in European general population), no significant differences were observed (p> 0.05). Thereafter, we did not investigate our hypothesis in a bigger sample of CLL patients since no mutations were found in our initial sample. Summary/Conclusion: Mutations of TNFRSF13B gene do not seem to participate in the pathogenesis and phenotype of CLL patients.
P1618: CLINICAL OUTCOME OF COVID-19 CONVALESCENT PLASMA TRANSFUSION IN CHRONIC KIDNEY DISEASE PATIENTS ON RENAL REPLACEMENT THERAPY WITH SEVERE TO CRITICAL COVID-19 DISEASE
Authors: J. Ahorro
Journal: HemaSphere (2022)

Background: Convalescent plasma therapy (CPT) has been explored for Coronavirus disease 2019 (COVID-19), but limited data exists for Chronic Kidney Disease (CKD) patients. Since the effects of COVID-19 therapies are still under study, CPT remains an option for these patients in the absence of other effective therapy. Aims: This study aimed to compare the clinical outcome of severe to critical COVID-19 patients with CKD on RRT who received COVID-19 CPT versus those who did not. Methods: Retrospective study. Primary outcome was clinical improvement defined as mortality or whether discharged alive or improvement in WHO 6-point severity scale within 28 days. Secondary outcomes include factors associated with clinical improvement such as CPT’s effect on pulmonary status, timing of CPT, effects on hematologic profile and inflammatory markers. Results: Total of 44 CKD patients were included. Half were given CPT, half were not. Mean age was 59±12.7 and 51±15.6 respectively; 68.2% male, 31.8% female. No significant difference was found in the clinical outcome of severe to critical COVID-19 CKD patients who received CPT and those who did not. However, significant reduction in HsCRP, procalcitonin and ferritin pre and post CPT was found. This provide support in the role of CPT in reducing the inflammatory cytokine course of COVID-19 in CKD patients. Image:Summary/Conclusion: Convalescent plasma transfusion did not show significant difference in the clinical outcome of severe to critical COVID-19 CKD patients, but was associated with decreasing trends of HsCRP, procalcitonin and ferritin, which are poor prognosticators of COVID-19 disease.
P1644: NOVEL VARIANTS IN GALE CAUSED SYNDROMIC MACROTHROMBOCYTOPENIA DISRUPTING THROMBOPOIESIS AND GLYCOSYLATION
Authors: A. Marin Quilez, C. A. Di Buduo, L. Díaz-Ajenjo, P. M. Soprano, E. Vuelta, I. Serramito-Gómez, S. Santos-Mínguez, C. Miguel-García, S. Tocino-Antonio, V. Palma-Barqueros, A. Zamora-Canovas, P. Ruiz-Sala, M. J. Peñarrubia, E. Pardal, J. M. Hernández-Rivas, J. R. González-Porras, R. Benito, J. Rivera, I. García-Tuñón, A. Balduini, J. M. Bastida
Journal: HemaSphere (2022)

Background: Glycosylation is recognized as a key process for proper megakaryopoiesis and platelet formation. The enzyme UDP-galactose-4-epimerase, encoded by GALE, is involved in protein glycosylation. There is currently scarce information about the performance of megakaryopoiesis in patients with thrombocytopenia associated with GALE variants. Aims: Assessing the clinical and platelet phenotype in three patients with syndromic macrothrombocytopenia associated to GALE variants, and to investigate the role of GALE in glycosylation and thrombopoiesis. Methods: Three patients from two unrelated families with lifelong severe thrombocytopenia, bleeding diathesis, mental retardation, mitral valve prolapse, and jaundice were enrolled in the Spanish Project of Inherited Platelet Disorders. Biallelic variants in GALE were identified by whole-exome sequencing (WES) (Figure 1). Platelet phenotyping included full blood count, blood film, light transmission aggregometry, flow cytometry analysis of major surface glycoproteins, and agonist-induced granule secretion. UDP-galactose-4-epimerase enzymatic activity was measured by HPLC/MS/MS. GALE and N-acetyl-galactosamine (LacNac) levels were evaluated by immunoblotting. Human megakaryocyte (Mk) culture from peripheral blood samples were assessed in one proband. Results: WES revealed four variants affecting GALE, three of them previously unreported (Figure 1). Patients showed giant and/or grey platelets, impaired platelet aggregation with several agonists, severely reduced alpha (P-selectin) and dense granule (CD63) secretion, and significant decrease of GPIbα-IX-V complex in the platelet surface. UDP-galactose-4-epimerase enzymatic activity was severely decreased in these patients. Immunoblotting showed reduced GALE in platelets and significant reduction of LacNAc, suggesting a hypoglycosylation pattern. In proband B.II.2, CD34+ derived Mks exhibited normal ploidy, and maturation, but impaired proplatelet formation. These Mks showed, similarly to patient platelets, normal surface levels of β3 integrin, but remarkable reduction in the glycosylation and externalization of GPIbα, and delocalization of vWF in the megakaryocyte membrane. Image:Summary/Conclusion: This study expands our knowledge on the GALE related thrombocytopenic disorder, emphasizing its critical role in platelet glycosylation, and providing further evidence that thrombocytopenia derives from altered proplatelet formation developing from GPIbα impairment. Funding PI20/00926, GRS2135/A/2020, GRS2314/A/2021, FMM AP172142019
P1615: AN ANALYSIS ACROSS ABO BLOOD GROUPS IN PATIENTS WITH COVID-19 INFECTION AND CORRELATION WITH HAEMATOLOGICAL BIOMARKERS, A SINGLE CENTRE STUDY
Authors: H. Shokr, M. Marwah, S. Marwah, F. Wandroo
Journal: HemaSphere (2022)

Background: The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the infectious disease coronavirus disease 2019 (COVID-19), has rapidly spread around the world and continues to be a global public health emergency. Currently worldwide over 5 million people have died due to this virus. Several studies observed that differences in blood groups may be linked to COVID-19 susceptibility and clinical outcomes; however, the results are controversial and there is a need for further research and validation. It is well known that ABO antigens are expressed on respiratory epithelial cells, however these antigens called type-1 antigens which differ from type-2 antigens expressed on red blood cells. Recent evidence has shown that receptor binding protein (RBD) of the SARS-CoV-2 binds preferentially to blood group A antigen on respiratory epithelial cells. Aims: This retrospective study aimed to analyse the haematological laboratory parameters and clinical manifestations in COVID-19 infected patients: we hypothesised that certain routine haematological indices may be altered in across the ABO blood groups, and that pattern identification would facilitate prediction of those at high risk of severe disease. Methods: A total number of 194 patient with COVID-19 confirmed by a real-time polymerase chain reaction (RT-PCR) were included in this study. Patients were classified into 4 groups according to their blood group (blood group A, 71 patients: blood group B, 30 patients; blood group AB, 8 patients and blood group O, 85 patients). Standard routine haematology laboratory indices were analysed for all the study participants. Results: Mortality rates were assessed in all four groups; of blood group A, 36.0% died, of blood group B, 25.65% died, of blood group AB, 23.5% died and of those with blood group O, 33.2% died. Deceased patients with blood group AB exhibited lower white blood cells, neutrophils, monocyte counts compared to patients with blood group A, B and O. Similarly, D-Dimer, urea, bilirubin, and C-reactive protein were significantly lower in the AB group compared to the rest of the blood groups. Positive correlations were found between Neutrophil/lymphocyte ratio and D-dimer and urea blood levels in all the study population (p=0.022, r=0.227 and p=0.254, r= 0.0001 respectively). Likewise, a positive correlation was found between neutrophil/ eosinophils ratio and blood urea, bilirubin, and C-reactive protein (p=0.047, r= 0.205; p=0.021, r= 0.249 and p= 0.0001, r= 0.377 respectively). Summary/Conclusion: This study observed patients with blood group AB have a lower risk of organ dysfunction or failure due to COVID-19. Although we found no significant statistical difference in mortality between different ABO groups, certain haematological indices and biochemical markers of inflammation were favourable in patients with blood group AB with a tendency to lower mortality.
PB2306: RELAPSE OF IMMUNE THROMBOCYTOPENIA AND MYOCARDITIS
Authors: F. Kapsouli, E. Sanidas, M. Mantzourani
Journal: HemaSphere (2022)

Background: Immune thrombocytopenia (ITP) is an acquired thrombocytopenia caused by autoantibodies against platelet antigens. ITP most often occurs within a few weeks following a viral infection, but it is also associated with other infections, drugs, hematopoietic malignancies and autoimmune diseases. Myocarditis is an inflammatory disease of cardiac muscle caused by a variety of infectious and noninfectious conditions. Autoimmune mechanisms have been implicated in the pathogenesis of myocarditis with or without a virus trigger. Aims: Our aim is to present an unusual case of myocarditis in a 17-year-old male, with a history of ITP presenting simultaneous relapse of ITP. Methods: A 17-year-old male with a history of ITP presented at the Emergency Department complaining of gingival bleeding, left shoulder pain and fever. Clinical examination showed extremity petechiaes and tachycardia, there was an ST elevation in V2-V6 leads on ECG and laboratory data included PLTs 2000/μL and elevated high sensitivity troponin (1.240pg/mL). He was treated immediately as a relapse of ITP with corticosteroids and he received b-blockers due to persistent tachycardia. Viral and immunological tests were negative. Results: Gradually, during hospitalization, there was an elevation of PLT count and a decrease in serum troponin levels with improving and finally normal ECG findings. The patient was discharged and continued treatment with prednisolone and b-blocker. He was reassessed after one month and troponin levels, PLT counts and ECG were normal. However, the cardiac Magnetic Resonance Imaging (MRI) revealed fibrosis with signal intensity and gadolium enhancement in the anterolateral and inferior segments. After three months a follow up cardiac MRI showed reduction of fibronitic tissue size. Summary/Conclusion: Autoimmunity plays a major role in the pathogenesis of both ITP and myocarditis. It seems that they share common autoimmune pathways and further research of which is important for understanding pathophysiology behind these clinical entities and improving their treatment.
Prevalence of Perinatal Depression and Anxiety in Both Parents
Authors: Kara L. Smythe, Irene Petersen, Patricia Schartau
Journal: JAMA Network Open (2022)

<h3>Importance</h3> New and expectant parents experience perinatal mood disorders, with consequences to parenting ability, bonding with the neonate, interpersonal relationships, and health and well-being of parents. Research shows that maternal and paternal perinatal mood disorders are associated, but no recent systematic review has addressed the prevalence of perinatal mood disorders in both mothers and fathers (parental dyad). <h3>Objective</h3> To examine the prevalence of perinatal mood disorders in parental dyads and identify factors associated with perinatal mood disorders in parental dyads. <h3>Data Sources</h3> Ovid (MEDLINE, Embase, and PsycINFO) and Web of Science were searched from January 1, 1990, to June 8, 2021, for observational studies reporting on the prevalence of perinatal depression or anxiety in a parental dyad. <h3>Study Selection</h3> Studies reporting the prevalence of anxiety or depression in both members of a parental dyad were included, with diagnosis according to established criteria (<i>Diagnostic and Statistical Manual of Mental Disorders</i>[Fifth Edition],<i>International Classification of Diseases, 11th Revision</i>) or use of validated screening tools. <h3>Data Extraction and Synthesis</h3> Prevalence data were extracted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were analyzed in subgroups: antenatal depression, early postnatal depression (0-12 weeks), late postnatal depression (3-12 months), and perinatal anxiety. Pooled prevalence was calculated using a random-effects meta-analysis model. Quality assessment was performed using Joanna Briggs Institute Appraisal Checklist for Studies Reporting Prevalence Data. Data were analyzed in June 2021. <h3>Main Outcomes and Measures</h3> Prevalence of perinatal anxiety and perinatal depression in parental dyads. <h3>Results</h3> Twenty-three studies were included, with data from 29 286 couples. The pooled prevalence of antenatal depression in both parents was 1.72% (95% CI, 0.96%-2.48%;<i>P</i> &lt; .001). The prevalence of early postnatal depression (up to 12 weeks post partum) was 2.37% (95% CI, 1.66%-3.08%;<i>P</i> &lt; .001) and the prevalence of late postnatal depression (3-12 months post partum) was 3.18% (95% CI, 2.3-4.05;<i>P</i> &lt; .001). Only 3 studies reported on perinatal anxiety in both parents, precluding a quantitative analysis. <h3>Conclusions and Relevance</h3> In up to 3.18% of couples, both parents may concurrently experience perinatal depression. Perinatal health care must consider the mental health needs of parents, both as individuals and as a parental dyad. Further research is needed to examine outcomes in families where both parents experience perinatal mood disorders.